Ultrasound Elastography

seminar LUT2, University of Kuopio, Finland

Josef Jaros jarosj@feec.vutbr.cz Dep. of Biomedical Engineering, FEEC, BUT Brno, CZ

1. Introduction
For centuries, physicians have used palpation as an important diagnostic tool. The efficacy of palpation is based on the fact that many diseases cause changes in tissue mechanical properties. These changes are caused either by exudation of fluids from the vascular system into the extra- and intracellular space or by loss of lymphatic systems, as in the case of cancer. The result is an increase in stiffness or elastic modulus of the tissue. For instance, during many abdominal operations, palpation is used to assess organs, such as the liver, and it is not uncommon for surgeons at the time of laparotomy to palpate tumors that were undetected preoperatively. These observations have provided the motivation for many investigators to seek a medical imaging technology that can estimate or assess the mechanical properties of tissues. Medical applications span a range from tumor detection to characterization of vascular plaques and assessment of vascular health to the study of skeletal muscle contraction, assessment of fetal lung maturity, and renal transplant rejection. Today, the most common approaches to static elasticity imaging employ an external stress stimulus applied through an imaging transducer or vascular balloon. Radio frequency (RF) signals have been used to measure object motion since the 1940s and the development of radar and sonar. In 1991, Ophir et al. used external compression methods to form strain images under static conditions and called the method elastography. Elastography, which is based on principal of physical elasticity, consists of applying a pressure on the examined medium and in estimating the induced strain distribution by tracking the tissue motion. In practical terms, RF ultrasonic data before and after the applied compression are acquired and speckle tracking techniques, e.g., cross correlation methods, are employed in order to calculate the resulting strain. The resulting strain image is called elastogram [3,4,7]. The primary goal of elastography was the identification and characterization of breast lesions.

2. Theory
2.1 Important quantities

Youngs modulus (E) describes longitudinal deformation in terms of strain (fractional change in length) in response to longitudinal stress (force per unit area). The shear modulus G relates transverse strain to transverse stress and is related to shear wave propagation in isotropic homogeneous media. The bulk modulus K of elasticity describes the change in volume of a material to external stress. Another physical property of isotropic inhomogeneous solids is the Poisson ratio , which is a ratio of transverse contraction per unit breadth divided by longitudinal extension per unit length [2].

One may ask the question, Which physical parameter corresponds most closely to the characteristics felt by palpation? In general, Poissons ratio of tissue has a value of between 0.49 and 0.499, which means tissue is nearly incompressible. (liquid incompressible medium has 0.5) . This leads to a simple result that Youngs modulus and the shear modulus of tissue are related by a scaling factor of three, that is, E=3G. The bulk moduli K of most soft tissues differ by less than 15% from that of water, even though the shear modulus varies over a huge range. Thus, shear and Youngs moduli, which have the widest dynamic range, are the most suitable elasticity parameters to measure and are probably the most closely associated with what is felt in palpation. The high water content of biological tissues means that they change shape easily when compressed but the volume is conserved. Consequently, K >> G, 0.5 and E = 3G.

2.2

The stress excitation methods

The excitation methods can be divided based on their temporal characteristics into two general groups: static methods and dynamic methods. In static methods, tissue is compressed slowly and the distribution of its displacement is measured in some way [e.g., with MR, ultrasound, or optically].The difficulty with the static method is that it requires knowledge of boundary conditions outside of the region under investigation. On the other hand, dynamic methods rely on the wave equation, which in its differential form is local in character. The excitation methods may also be grouped based on the spatial characteristics of the excitation. External methods apply a stress, or a compression force, on the skin to deform the tissue beneath. This is often done by a simple mechanical means, such as pressing and holding a plate on the skin (in static approach) or vibrating the skin using a vibratory device (in dynamic approach). Internal excitation methods apply the exc itation internally and directly on the region of interest within tissue. Both static and dynamic excitations are possible with the radiation force of ultrasound. Biological sources, such as breathing or cardiovascular pulsation, are other means for internal excitation of tissue. Ultrasound displacement methods are based on either Doppler measurements or simple displacement measurement using pulse-echo methods [2,3].

Fig. 1: Stress-strain curves acquired for five types of breast tissue: normal fat, normal glandular, ductal carcinoma in situ, benign fibrotic lesion, and infiltrating ductal carcinoma [2]

2.3

Principle of elastography

Application of 1D ultrasound signals before and after compression and consequently changes of reflected signal are clear from figures 2 and 3.

Fig.2: The principle of Elastography: The tissue is insonified a) before and b) after a small uniform compression. In the harder tissues (e.g. the circular lesion depicted) the echoes will be less distorted than in the surrounding tissues, denoting thus smaller strain [3].

If one or more of the tissue elements has a different stiffness parameter than the others, the level of strain in that element will generally be higher or lower; a stiffer tissue element will generally experience less strain than a softer one [3,8]. Fig. 3 shows a schematic representation of the time delay and strain computation process. The windows are usually translated in small overlapping steps along the temporal axis of the echo line, and the calculation is repeated for all depths.

Fig. 3: A schematic showing the process of computing the strain in a tissue segment. Congruent windowed segments of the pre-compression and post-compression signals are compared by cross correlation. While the early windowed segments exhibit virtually no delay, a finite delay (designated del (t)) is detected between the later segments [4]

The strain is computed as the gradient of the time delay (or displacement), i.e. Strain = del (t) /T, where T is the initial (pre-compression) separation between the windowed segments [4].

3. Methods
3.1 Intravascular ultrasound elastography
Intravascular ultrasound elastography is a technique that assesses the local strain in the artery wall and plaque. For intravascular purposes, the compression can be obtained from the systemic pressure difference that is already available in intravascular applications. Additionally, well-controlled deformation is possible by using a transducer positioned in a compliant intravascular balloon [5]. Principle The principle of intravascular elastography is illustrated in figure 4. An ultrasound image of a vessel-phantom with a hard vessel wall and a soft eccentric plaque is acquired at a low pressure . In this case, there is no difference in echogenicity between the vessel wall and the plaque resulting in a homogeneous IVUS echogram. A second acquisition at a higher intraluminal pressure (pressure differential is approximately 5 mmHg) is performed. The elastogram (image of the radial strain) is plotted as a complimentary image to the IVUS echogram. The elastogram reveals the presence of an eccentric region with increased strain values thus identifying the soft eccentric plaque.

Fig. 4: Echogram (left) and elastogram (right) of a vessel mimicking phantom containing an isoechoic soft lesion between 7 and 11 oclock. The lesion is invisible in the echogram, while it is clearly depicted in the echogram [5].

Detection Technique The deformation is obtained using cross-correlation analysis. First the boundary between lumen and vessel-wall is determined. Next the signal is divided into windows representing e.g. 300 microns of tissue. The windows have an overlap of 50%. Each window of the signal acquired at the low intra-luminal pressure is cross-correlated with the corresponding window of the signal acquired at the high intra- luminal pressure. The position of the peak of the cross-correlation function corresponds with the displacement of the tissue. If the displacement for all windows is known, the differential displacement between successive windows is determined. After normalizing for the window length and overlap, the strain is obtained.

The calculation of the time delay as a function of echodepth is illustrated in fig 5. In the upper part of the figure, subsequent windows of 50 sampling points of both the rf traces are shown. In this figure both traces are interpolated and the second scan is preshifted for improved visual inspection of the shape of the signals. Comparison of the 2 signals, before and after compression, shows that the correlation between the signals is high, thus allowing the use of the proposed technique. The cross correlation function was estimated using these windows of the two traces and are shown in the bottom part of the figure. Comparison of the subsequent cross correlation function windows in echodepth shows a decreasing position of the peak of this function, due to the compression of the material. The radial strain profile is calculated using a one dimensional finite difference algorithm, [5].

Fig. 5: Principle of time delay estimation using the peak of the crosscorrelation coefficient function. In the upper part, both the rf -traces (with the 2nd trace preshifted for better visual comparison) are shown for windows with increasing echodepth. In the lower part, the corresponding crosscorrelation coefficient function for each window is plotted, showing a decreasing position of the peak with increasing echodepth [5].

3.2 Palpography
Intravascular ultrasonic palpation is a one-dimensional elasticity imaging technique, which was developed to measure the elastic properties of vascular tissues within the inner layer of the arterial wall. The technique has the distinct advantage of being simple enough to be implemented in realtime using relatively inexpensive hardware [5]. General Principle The technique is similar to intravascular elastography. However, compound images that are known as strain palpograms are created by colour coding the measured radial strain profile and superimposing it on the IVUS echogram at the lumen vessel interface, as illustrated in figure 6.

a)

b)

Fig. 6: Examples of strain palpograms corresponding to an elastically homogeneous vessel phantom. Showing the strain palpograms produced using pressure differences of a) 2mmHg and b) 7 mmHg.[5]

4. Experiments and models

The example of measuring system is shown in fig. 7. The experimental set-up consists mainly of a clinical ultrasound scanner working with a 7.2 MHz probe and of a controlled step compression device. The latter is composed of a positioning slider, vertically mobile, on which is fixed the ultrasound probe, [1].

Fig. 7: Scheme of the instrumental set-up for elastographic experiments with external ultrasound [1].

4.1 Phantoms
A foam pha ntom (fig.8) has first been used, containing within its centre a spherical hard inclusion of approximately 1.5 cm diameter and made from a solution of agar-agar. This phantom is characterised by an acoustical homogeneity and a compressible mechanical behaviour.

Fig. 8: Experimental result from a foam (a) Phantom schematic cross-section, (b) Classical B-mode image of the ROI displayed with a logarithmic grey scale, (c) Resulting elastogram computed with 1-mm window length with 60% overlap and (d) Strain distribution investigation with finite element modellin g [1]

Whereas the hard inclusion is not visible on the ultrasound image, it is clearly brought out in the elastogram with sharp boundaries. The next experimental object is a 3-layer gel based phantom (fig.9), made from a mixture of agar and gelatin. The top and the bottom layers have the same stiffness and the middle one is softer.

Fig. 9: Experimental result from a 3 layer tissue mimicking agar-gelatine phantom (a) Phantom schematic cross-section. (b) Classical B-mode image of the ROI displayed with a logarithmic grey scale, (c) Resulting elastogram computed with a 1-mm window length with 60% overlap and (d) Strain distribution investigation with finite element modelling [1].

Whereas no acoustical difference has been introduced between layers, these latter are clearly distinguished in the elastogram with well defined boundaries [1].

4.2 Experiments for intravascular ultrasound

The experiments are done on intravascular phantoms too [1]. The method is explained above.

Fig. 10: Experimental result from a 2 layer cryogel phantom (a) Phantom schematic cross-section. The inner layer-the softer, whereas the outer layer-the harder (b) Classical ultrasound image, (c) Elastogram

computed with a 0.25-mm window length with 80% overlap, and (d) Strain distribution investigation with finite element modelling [1].

4.3 Experiments in vivo

The results of ultrasound elastography experiments in vivo are similar as in vitro and are quite well described in many references, e.g. [4,6,7].

Fig. 11: Sonogram and elastogram pairs from fibroadenoma and infiltrating ductal carcinoma (Garra et at. 1997) of the breast in vivo at 5 MHz. Observe the clear depiction of the carcinoma on the elastogram (inclu ding the distal margins), as well as the size discrepancy between the sonographic and elastographic appearance of the carcinoma [4].

Very good results were obtained in intravascular elastography experiments with Yucatan pigs, [6]. Authors refer: - Analysis revealed a sensitivity and specificity of 100% and 80% respectively, to identify fatty plaques. The presence of a high strain spot (strain>1%) has 92% sensitivity and 92% specificity to identify macrophages. - High correlation between the strain in cap of coronary plaques and the amount of macrophages and an inverse relation between the amount of smooth muscle cells and strain.

Conclusions
Ultrasound elastography is well developing method and can be used in wide range of medical applications, however much progress has yet to be made in order for elastography to become a viable clinical and investigational tool.

References:
[1] Brusseau E., et al. Local Estimation of RF Ultrasound Signal Compression for Axial Strain Imaging : Theoretical Developments and Experimental Results, IEEE Engineering in Medicine and Biology Magazine 21(4), July/August 2002, p. 86-94 [2] Greenleaf, J.F., et al, Selected Methods for Imaging Elastic Properties of Biological tissues, Annual Reviews of Biomedical Engineering, 2003. [3] Konofagou E. E., et al, Elastography: From theory to clinical applications, Summer Bioengineering Conference, June 25-29, Florida, 2003 [4] Ophir J., et al. Elastography: Imaging the Elastic Properties of Soft Tissues with Ultrasound. Journal of Medical Ultrasonics, Vol.29, 2002.

Internet pages: [5] Korte, C.L., et al., IVUS Elastography: Technique, http://www2.eur.nl/fgg/thorax/elasto/technique.html [6] Korte, C.L., et al., Identification of Atherosclerotic Plaque Components With Intravascular Ultrasound Elastography In Vivo: A Yucatan Pig Study, http://circ.ahajournals.org/cgi/content/full/105/14/1627 [7] Ophir, J., New medical imaging technique improves chances of early cancer detection, http://www.algor.com.cn/example/medical006.htm [8] Research and Applications Center in Image and Signal Processing: Elastography http://www.creatis.insa-lyon.fr/menu/iultrasonore/demos/demo-elastography/index-us.html#animation

Note:

1 mmHg = 133,322 Pa (Pascal), 1 atm = 760 mmHg = 101,325 kPa